Predictors of Cardiovascular and Gastrointestinal Disorders, Inappropriate Nonsteroidal Anti-inflammatory Drug Use, and Alzheimer’s Disease and Related Dementia in Older Adults with Osteoarthritis

Evidence from some studies suggest that osteoarthritis (OA) patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that are not in accordance with their cardiovascular (CV) or gastrointestinal (GI) risk profiles. However, no such study has been carried out in the United States. Therefore, we sought to examine the prevalence and predictors of potentially inappropriate NSAIDs use in older adults (age > 65) with OA using machine learning with real-world data from Optum De-identified Clinformatics® Data Mart. We identified a retrospective cohort of eligible individuals using data from 2015 (baseline) and 2016 (follow-up). Potentially inappropriate NSAIDs use was identified using the type (COX-2 selective vs. non-selective) and length of NSAIDs use and an individual’s CV and GI risk. Predictors of potentially inappropriate NSAIDs use were identified using eXtreme Gradient Boosting. Our study cohort comprised of 44,990 individuals (mean age 75.9 years). We found that 12.8% individuals had potentially inappropriate NSAIDs use, but the rate was disproportionately higher (44.5%) in individuals at low CV/high GI risk. Longer duration of NSAIDs use during baseline (AOR 1.02; 95% CI:1.02–1.02 for both non-selective and selective NSAIDs) was associated with a higher risk of potentially inappropriate NSAIDs use. Additionally, individuals with low CV/high GI (AOR 1.34; 95% CI:1.20–1.50) and high CV/low GI risk (AOR 1.61; 95% CI:1.34–1.93) were also more likely to have potentially inappropriate NSAIDs use. Heightened surveillance of older adults with OA requiring NSAIDs is warranted.

Inappropriate nonsteroidal anti-inflammatory drug (NSAID) use can occur by using more than one prescription or over-the-counter NSAID or exceeding the manufacturer's recommended dosage. There are risks associated with inappropriate NSAID use; however, the prevalence and predictors of inappropriate NSAID use are unknown. The study objectives are to estimate the prevalence of inappropriate NSAID use and identify characteristics associated with inappropriate use. We identified 6877 patients at 2 Veterans Affairs Medical Centers through pharmacy records who filled 3 or more NSAID prescriptions in 6 months. We randomly selected 2535 patients and mailed them a survey about NSAIDs, gastroprotective medications, gastrointestinal (GI) symptoms, and pain. Inappropriate NSAID users either took 2 or more NSAIDs for 3 days or more or exceeded the maximum daily recommended dosage of 1 or more NSAID in the past week. Data were also collected from medical records. Approximately 1572 patients (62%) returned the survey, and 1250 reported NSAID use in the past week. Approximately 32% (n = 400) used NSAIDs inappropriately, including taking 2 or more NSAIDs (n = 173), exceeding the highest daily recommended dosage (n = 161) or both (n = 66). Being a minority (odds ratio = 1.62, P < 0.001) and having an income of $20,000 (odds ratio = 1.70, P < 0.001) or lesser both predicted inappropriate NSAID use. Inappropriate NSAID use was associated with more GI symptoms (β = 0.57, P < 0.001) and higher levels of pain (β = 0.85, P < 0.001). Inappropriate NSAID use is prevalent. Providers should consider counseling all patients about NSAID use, especially patients with GI problems or pain problems.

Mammographic density has been established as a strong risk factor for breast cancer while use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) has been associated with a reduction in risk of breast cancer. The hypothesis is that NSAIDs reverses the expression of prostaglandin E2, thereby reducing the local production of estrogens. This report describes the differences in mammographic densities by duration of NSAID use in a multiethnic population. Information for this analysis was available from two previous investigations: a nutritional intervention study with 218 women and a nested case-control study of breast density with 1274 women. On the basis of self-reported medication use from a questionnaire common to both investigations, women were categorized into no use, up to 1 year, 2-5 years, 6-10 years, and 11+ years. Screening mammograms were assessed for density using a computer-assisted method. We applied general linear models to calculate mean percent densities for each medication use category while adjusting for covariates. The analysis of the overall study population did not show a significant association between total NSAID use and mammographic density. Contrary to our hypothesis, women with long-term total NSAID use had non-significantly higher densities than non-users. In addition, the results differed by menopausal status. Whereas the trend of higher densities with longer duration of total NSAID use was significant among postmenopausal women, breast density was slightly lower among premenopausal women with long-term NSAID use. Experimental studies need to be performed to study the effect, if any, of NSAID use on breast density.

Background: Studies suggest that non-steroidal anti-inflammatory drug (NSAID) use may increase risk of renal cell cancer (RCC), but the relationship to the lethal form of RCC remains unknown. Methods: We examined the relationship between NSAID use and RCC risk in two large prospective cohorts: the Nurses’ Health Study and the Health Professionals Follow-up Study. Use of aspirin and other NSAIDs was ascertained in 1990 in the Nurses’ Health Study and in 1986 in the Health Professionals Follow-up Study, and every 2 years thereafter. We evaluated baseline use and duration of NSAID use. We defined the lethal form of RCC as RCC that resulted in death due to the disease. Results: During follow-up of 18 years among 77,524 women and 20 years among 49,403 men, we documented 364 cases of RCC, of which 102 were fatal. Regular use of non-aspirin NSAIDs was associated with an increased overall RCC risk; there was a dose-response relationship between duration of non-aspirin NSAID use and RCC risk; compared with non-regular use, the pooled multivariable relative risks (RRs) were 0.78 (95% CI, 0.58-1.06) for use of less than 4 years, 1.29 (95% CI, 0.95-1.74)) for 4 to less than 10 years, and 2.21 (95% CI 1.39-3.49) for use for 10 or more years (P for trend, 0.0006). Furthermore, non-aspirin NSAID users of 4-10 years (pooled multivariable RR 3.13, 95% CI 1.70-5.77) and more than 10 years (pooled multivariable RR 7.23, 95% CI 2.51-20.83) had a significantly increased risk of lethal RCC. Aspirin use was not associated with increased risk of overall (pooled multivariable RR 1.07, 95% CI 0.84-1.34) or lethal RCC (pooled multivariable RR 1.59, 95% CI 0.85-2.96). Conclusion: Our prospective data suggest that non-aspirin NSAID use is associated with an increased incidence of RCC, especially the lethal form of RCC. Citation Format: Mark A. Preston, Jed-sian Cheng, Glen Barrisford, Alex Sanchez, Adam S. Feldman, Dayron Rodriguez, Toni K. Choueiri, Meir Stampfer, Walter C. Willett, Eunyoung Cho. Nonsteroidal anti-inflammatory drug (NSAID) use and risk of lethal renal cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-279. doi:10.1158/1538-7445.AM2014-LB-279

Long-Term Preoperative Nonsteroidal Anti-inflammatory Drug Use Does Not Impact Revision Rate After Repair of Rotator Cuff, Achilles, Distal Biceps, or Quadriceps Tendon

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To compare the prevalence of potentially inappropriate non-steroidal anti-inflammatory drugs (NSAIDs) among NSAIDs users defined with frequently used potentially inappropriate medication (PIM) lists and to identify the determinants of their use. Cross-sectional survey among community-dwelling older adults from Germany. N = 284 NSAIDs users aged 65-89 years. All currently regularly or as-needed used drugs were recorded during a home visit. Multivariate logistic regression models were applied to assess the potential determinants of potentially inappropriate NSAIDs use. Prevalence of potentially inappropriate NSAIDs use was 54.2%, 45.4%, 29.9%, 20.4%, and 3.5% when applying the STOPP, 2019 Beers, EU(7)-PIM, FORTA, and PRISCUS list, respectively. No study participant was identified as a potentially inappropriate NSAIDs user by all five lists simultaneously. The majority (68%) were identified only by one or two lists. Merely the STOPP and Beers criteria had a moderate inter-instrument agreement. Lower pain severity, gout, peptic ulcer (PU), cardiovascular disease (CVD), and chronic kidney disease (CKD) were statistically significantly associated with potentially inappropriate NSAIDs use defined by the STOPP criteria and the latter three conditions also with the 2019 Beers criteria. The STOPP and Beers criteria may be superior to the other lists because they more frequently identify potentially inappropriate NSAIDs use in conditions implying a high risk for NSAIDs' adverse events (i.e., PUD, CKD and CVD). We developed a harmonized, country-independent PIM list for NSAIDs with the same advantages as observed for the STOOP and 2019 Beers criteria and recommended its use.

THU0624 UNDERSTANDING ETHNIC DIFFERENCES IN THE UTILIZATION OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS FOR OSTEOARTHRITIS

This Month in Gastroenterology

A Narrative Review:The use of the topical nonsteroidal anti-inflammatory drugs (NSAID) ibuprofen for the treatment of knee osteoarthritis. Supporting clinician decision-making in the first-line treatment of osteoarthritis.Objective:To open discussion at a clinical level on the guidelines for the pharmacological management of osteoarthritis of the knee, this narrative review looks into the use of topical NSAID being a clinically effective, safe, and cost-efficient treatment compared to an oral alternative.Background:With the over prescription of NSAIDs in the age of above 65 years, there has been a call for increased restrictions of the sale of oral preparations of NSAIDs. It is our view that there is still a lack of awareness in the benefit of topical NSAIDs to the patient (no evidence of adverse reactions recorded by the Joint Formulary Committee [JFC] to date) as well as provider (topical application is cheaper as a National Health Service [NHS] prescription).Methods:Key online resources included PubMed, Athens, Cochrane Library, Google Scholar, MEDLINE, and relevant clinical and commissioning guidelines with the final date of data collection in March 2017. We also contacted the manufacturer and license holder directly for further clarification. Randomized, double-blind control studies, commissioned reports, International Guidelines, MEHA Guidelines, and license holder data were included. Where possible studies included had to have fair randomization and adhere to key treatment pathways as highlighted by National Institute for Health and Clinical Excellence (NICE) and other guidelines.Discussion:Current guidelines advise that patients who seek initial treatment of osteoarthritis of the knee should consider a combination of treatment modalities, including pharmacological therapies, particularly the use of NSAIDs. At a clinical level, a reoccurring issue identified with this advice is the inappropriate use of oral NSAIDs, and the concern that the risks associated with ease of access (“over the counter”), and overuse, may result in systemic adverse events in this cohort of patients. Multiple studies have examined the negative effect of oral NSAIDs and the associated risks of use. We were unable to source studies that showed any adverse systemic events from the use of topical NSAIDs; however, there are good quality trials comparing oral to topical NSAIDs, showing similar levels of efficacy at 6 and 12 weeks.Conclusion:Topical NSAIDs provide good levels of pain relief in subjects with mild to moderate knee osteoarthritis. There is also evidence for the use of the topical application being a clinically effective, safe, and cost-efficient treatment.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have emerged as potential chemopreventive agents for melanoma. However, the clinical studies have provided contradictory results as to whether NSAIDs reduce the risk of melanoma. Our aim was to assess this association through a detailed meta-analysis of the studies on the subject published in the peer-reviewed literature. Relevant studies were identified by searching PubMed, EMBASE and Web of Science electronic databases up to July 2012. Reference lists from retrieved articles were also reviewed. Pooled relative risk (RR) estimates and corresponding 95% confidence intervals (CIs) were calculated using the fixed-effects or the random-effects models on the basis of heterogeneity analysis. Subgroup analyses were carried out where data were available. Ten studies involving 490 322 participants contributed to the meta-analysis. The summary RR estimate on the basis of all studies did not indicate that overall NSAIDs use significantly decreases the risk of melanoma (RR=0.94; 95% CI, 0.86-1.03). The use of neither aspirin (RR=0.96; 95% CI, 0.89-1.03) nor nonaspirin NSAIDs (RR=1.05; 95% CI, 0.96-1.14) was associated with the risk of melanoma. Similar results were obtained in the subgroup analyses of cohort studies (RR=1.03; 95% CI, 0.95-1.13), high-intensity NSAID use (the highest dose of NSAID use reported by included studies, RR=1.05; 95% CI, 0.79-1.40), and long-term NSAID use (longest duration of NSAID use reported by included studies, RR=0.87; 95% CI, 0.66-1.14). However, a slight reduction in the risk of melanoma by taking NSAIDs was observed in case-control studies (RR=0.86; 95% CI, 0.80-0.93). In conclusion, the results of our meta-analysis did not indicate that the use of NSAIDs or aspirin is associated with the risk of melanoma. More and in-depth research should focus on those problems in the future.

Background and Objectives: Self-medication and inappropriate use of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics are major public health concerns, particularly in settings with variable access to healthcare. Understanding patterns of medication use and renal risk perception can inform targeted interventions. This study examined NSAID and antibiotic use, self-medication behaviors, and renal risk awareness among Romanian primary care patients, with attention to urban-rural differences. Materials and Methods: A cross-sectional survey was conducted among 201 primary care patients (101 rural, 100 urban). Data on NSAID and antibiotic use, self-medication practices, sources of recommendation, and renal risk perception were collected using a study-specific questionnaire. Multivariable logistic regression was applied to identify predictors of frequent NSAID use, inappropriate antibiotic use, self-medication frequency, and high perceived renal risk. Results: NSAID use was nearly universal (95%), with frequent use strongly associated with non-professional recommendations. Antibiotic misuse was more common in rural participants and largely driven by informal acquisition. Self-medication patterns differed by residence: rural participants reported system- or access-related reasons and reliance on non-professional sources, while urban participants engaged in frequent, convenience-driven self-medication. Although most participants were aware of potential renal harm, this did not consistently lead to safer behaviors. Higher educational level and trust in healthcare professionals predicted increased perceived renal risk, whereas rural residence was associated with lower risk perception. Conclusions: Medication misuse is influenced more by recommendation sources, access barriers, and trusted information pathways than by knowledge alone. Interventions should focus on improving professional guidance, addressing informal recommendation networks, and tailoring strategies to urban-rural contexts.

Pain is a common symptom among patients with kidney disease. However, little is known about use of analgesics among patients aged 65 years or older with chronic kidney disease (CKD) who do not receive dialysis treatment. To assess national trends and geographic variations in use of opioids and prescription nonsteroidal anti-inflammatory drugs (NSAIDs) in older adults with and without CKD in the US (2006-2015) and examine associations between use of opioids and patient outcomes. This cohort study used the 5% Medicare claims data (2005-2015) to select 10 retrospective annual cohorts of Medicare Part D beneficiaries aged 65 years and older from 2006 to 2015 and a retrospective longitudinal cohort. Data were analyzed in August 2019. CKD status and other comorbidities identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Analgesic use was measured by overall use (proportion of ever used opioids/NSAIDs), long-term use (prescribed >90 days), and cumulative use (total annual days' supply). Patient outcomes included progression to end-stage kidney disease (ESKD) and all-cause mortality. A total of 6 260 454 beneficiaries (9.6% identified with CKD by claims) were selected in the annual cohorts and 649 339 beneficiaries (8.3% identified with CKD) were selected in the longitudinal cohort. There was significant growth in opioid use (31.2%-42.4%) and NSAID use (10.7%-16.6%) among patients aged 65 years and older with CKD from 2006 to 2015. Long-term use of opioids increased during 2006 to 2014 (25.8%-36.7%) but decreased through 2015 at 35.6%, while long-term use of NSAIDs remained stable. Opioid use was higher in patients with CKD, particularly CKD stages 4 to 5 (odds ratio [OR], 1.35; 95% CI, 1.33-1.37; P < .001) compared with non-CKD. NSAID use was lower in patients with CKD stages 4 to 5 (OR, 0.55; 95% CI, 0.54-0.56; P < .001). Substantial geographic variations in analgesic use were observed across states (opioid use in CKD: 24.7%-54.3%; NSAID use in CKD: 11.2%-20.8%, 2012-2015). Opioid use was associated with progression to ESKD (hazard ratio [HR], 1.10; 95% CI, 1.04-1.16; P = .001) and death (HR, 1.19; 95% CI, 1.18-1.20; P < .001) independent of CKD status and other covariates. There was an inverse association between NSAID use and death (HR, 0.84; 95% CI, 0.83-0.85; P < .001). Among Medicare patients with CKD, use of prescription analgesics, both opioid and NSAID, increased from 2006 to 2015. Optimizing pain management in a complex condition such as kidney disease should remain a priority for clinicians and researchers alike.

AB0292 EFFECTS OF ACETAMINOPHEN ON THE KIDNEY FUNCTIONS OF PAITIENTS WITH MUSCULOSKERLTAL DISEASE TREATED WITH LONG-TERM NONSTEROIDAL ANTI-INFRAMMATORY DRUG THERAPY

NSAIDs, Risks, and Gastroprotective Strategies: Current Status and Future